Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus.
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| Abstract |
Type I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Using a novel protocol we generated 1,132 aptamer-based protein measurements from anti-dsDNApos SLE blood samples and derived an IFN protein signature (IFNPS) that approximates the IFN 21-gene signature (IFNGS). Of 82 patients with SLE, IFNPS was elevated for 89% of IFNGS-high patients (49/55) and 26% of IFNGS-low patients (7/27). IFNGS-high/IFNPS-high patients exhibited activated NK, CD4, and CD8 T cells, while IFNPS-high only patients did not. IFNPS correlated with global disease activity in lymphopenic and non-lymphopenic patients and decreased following type I IFN neutralisation with anifrolumab in the SLE phase IIb study, MUSE. In summary, we developed a protein signature that reflects IFNGS and identifies a new subset of patients with SLE who have IFN activity.
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| Authors | Michael A Smith, Chia-Chien Chiang, Kamelia Zerrouki, Saifur Rahman, Wendy I White, Katie Streicher, William A Rees, Adam Schiffenbauer, Lisa G Rider, Frederick W Miller, Zerai Manna, Sarfaraz Hasni, Mariana J Kaplan, Richard Siegel, Dominic Sinibaldi, Miguel A Sanjuan, Kerry A Casey |
| Journal | Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 4462 (03 10 2020) ISSN: 2045-2322 [Electronic] England |
| PMID | 32157125 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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